Six-year follow-up from the weekly-three-weekly study comparing cisplatin once-a-week to once-every-three-weeks as concurrent chemoradiation for locally advanced head and neck squamous cell carcinoma.
Authors: Vanita Noronha, Vijay Maruti Patil, Nandini Sharrel Menon, Ajaykumar Singh, Sunil Ramdhan Chopade, Sarbani Ghosh Laskar, Jaiprakash Agarwal, Tejpal Gupta, Ashwini Budrukkar, Vedang Murthy, Neha Mittal, Asawari Patil, Munita Bal, Abhishek Mahajan, Suman Kumar, Vijayalakshmi Mathrudev, Kavita Prakash Nawale, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

6071 Background: In the weekly-3-weekly (W3W) study, cisplatin at 100 mg/m 2 once-every-3-weeks led to superior locoregional control compared to cisplatin 30 mg/m 2 once-a-week in combination with radical radiation for locally advanced head and neck squamous cell carcinoma (LAHNSCC). We report the updated analysis of the study. Methods: In this phase III open label non-inferiority study conducted between 2013 and 2017, 300 patients with LAHNSCC were randomly assigned to receive cisplatin 100 mg/m 2 once-in-3-weeks or cisplatin 30 mg/m 2 once-a-week, concurrently with radiation. The primary endpoint was locoregional control. Secondary outcomes included progression free survival (PFS), overall survival (OS), toxicity, and quality of life. Results: As of February 5, 2022 (median follow-up, 77.3 months), 132 patients (44%) have had an event for locoregional recurrence; 75 (50%) in the once-a-week cisplatin arm and 57 (38%) in the once-every-3-weeks cisplatin arm. The updated estimated cumulative 2-year locoregional control rates were 59.3% and 75.3% in the once-a-week and once-every-3-weeks cisplatin arms, respectively; absolute difference, 16% (95% CI, 7.19 to 24.81). The estimated 5-year locoregional control rates were 48.2% and 55.2% in the once-a-week and once-every-3-weeks cisplatin arms respectively; absolute difference, 7% (95% CI, -2.5 to 16.5). The median time to locoregional failure was 46.1 months (95% CI, 31.63 to 60.56) in the once-a-week cisplatin arm, and 57.9 months (95% CI, 47.1 to 68.6) in the once-every-3-weeks cisplatin arm; HR, 1.43 (95% CI, 1.01 to 2.02); P = 0.042. The estimated median PFS was 17.5 months (95% CI, 0 to 38.31) in the once-a-week cisplatin arm, versus 37.5 months (95% CI, 28.45 to 46.45) in the once-every-3-weeks cisplatin arm; HR, 1.13 (95% CI, 0.85 to 1.5); P = 0.41. Events for OS included 173 (57.7%) deaths; 109 (36.3%) patients are alive, and 18 (6%) are lost to follow-up. The 5-year OS in the once-a-week and once-every-3-weeks cisplatin arms were 43.1% and 48.6%, respectively. Estimated median OS was 38.5 months (95% CI, 16.3 to 60.7) in the once-a-week cisplatin arm, versus 57.3 months (95% CI, 38.6 to 75.9) in the once-every-3-weeks cisplatin arm; HR, 1.19 (95% CI, 0.89 to 1.6); P = 0.238. Details regarding chronic toxicities and second primaries will be presented. Conclusions: Long term follow-up confirms that cisplatin at 100 mg/m 2 administered once-every-3-weeks concurrently with radical radiation for LAHNSCC leads to superior locoregional control and should remain the standard of care. The study was not powered to test for a difference in OS; OS was numerically higher in the once-every-3-weeks cisplatin arm, but the difference did not attain statistical significance. Clinical trial information: CTRI/2012/10/ 003062.